The purpose of this project is to investigate the mechanism by which ethionine interferes with methionine metabolism in the secretory processes of the rat parotid gland acinar cell. The effect of energy depletion on: (1) the secretory granule, (2) release of the normal secretory product, (3) release of an abnormal product (crystalloid) will be determined by pretreating rats with isoproteranol. Morphological changes will be determined by observation with electron microscopy. Ethionine substitution for methionine and any induced variations in the amino acid composition of the normal and abnormal secretory products will be determined by isolation and amino acid analysis. The mechanism of formation and the fate of the 'crystalloids' will be determined using an appropriate radioactive precursor (leucine-H). Animals will be sacrificed sequentially and tissue subjected to autoradiographic analysis at the ultrastructural level. Methionine plays a critical role in salivary gland synthesis and secretion because of its metabolic roles in: (1) the generation of intracellular energy and (2) protein synthesis. The proposed studies will permit a better understanding of the role of methionine in protein synthesis and secretion. By establishing a model for altering the composition of saliva, it will be possible to study related alterations in the oral environment and in the incidence of dental disease.